Thus, using mice lacking the ORL1 receptor and their wild-type littermates, the present study assessed the role Selleckchem Verubecestat of the ORL1 receptor in psychomotor stimulant and rewarding actions of buprenorphine and morphine. Morphine (5, 10 mg/kg) dose-dependently increased motor activity and induced conditioned place preference. However, the magnitude of each response was comparable for the mutant mice and their

wild-type littermates. In contrast, buprenorphine (1 mg/kg) induced greater motor stimulation in ORL1 receptor knockout mice as compared with their wild-type littermates. Further, single conditioning with buprenorphine (3 mg/kg) induced place preference Gamma-secretase inhibitor in mutant mice but not in their wild-type littermates. The results of binding assay showed that buprenorphine concentration-dependently (0-1000 nM) displaced specific binding of [H-3]-OFQ/N in brain membrane of wild-type mice. Together, the present results suggest that the ability of buprenorphine to interact with the ORL1 receptor modulates its acute motor stimulatory and rewarding effects. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Stimulation Of

kappa-Opioid receptors in the substantia nigra pars reticulata (SNPR) increases the locomotor activity of young rats: an effect blocked by systemic administration of a D2-like next receptor agonist. Based on these initial findings, we proposed that: (a) D2-like receptors in the dorsal striatum are responsible for attenuating kappa-opioid-induced locomotor activity, and (b) the effects of D2-like receptor stimulation are mediated by the indirect pathway, which extends from the dorsal striatum to the SNPR via the globus pallidus (GP) and subthalamic nucleus (STN). To test the first hypothesis, young rats were given a systemic injection (i.p.) of saline or the K-Opioid receptor agonist (+/-)-trans-U50,488 methanesulfonate salt

(U50,488) on postnatal day (PD) 18. Later in the testing session, rats received bilateral infusions of vehicle or the D2-like receptor agonist R(-)-propyinorapomorphine (NPA) into the dorsal striatum, and the ability of NPA to block U50,488-induced locomotor activity was determined. To test the second hypothesis, rats were given sham or bilateral electrolytic lesions of the GP or STN on PD 16. Two days later, saline- and U50,488-induced locomotor activity was measured after systemic (i.p.) administration of vehicle or NPA. As predicted, dorsal striatal infusions of NPA attenuated the U50,488-induced locomotor activity of young rats. Contrary to our expectations, bilateral lesions of the GP or STN did not impair NPA’s ability to block U50,488-induced locomotor activity.